Behavioral and Neurobiological Outcomes in the Reserpine-Induced Fibromyalgia-like Model in Rodents: A Scoping Review

Background: Fibromyalgia (FM) is a chronic nociplastic pain condition characterized by widespread pain and non-nociceptive symptoms. The reserpine-induced model is widely used to investigate FM-like phenotypes in rodents, but methodological heterogeneity may affect phenotype expression and reproducibility. Objective: This scoping review intended to identify published research that involved behavioral and neurobiological outcomes of reserpine-induced FM-like conditions and identify factors underlying phenotypic variability. Eligibility criteria: Eligible studies were experimental studies in rats or mice using reserpine-based protocols and reporting affective, cognitive, or neurobiological outcomes. Sources of evidence: Four databases (PubMed, Embase, Web of Science, and Scopus) were assessed. The search strategy was not restricted by publication date. Charting methods: Study selection and data extraction were independently performed by two reviewers, and methodological quality was assessed using SYRCLE. Results: This review shows that study heterogeneity is further increased by species, strain, sex, reserpine dose and administration regimen, vehicle composition, outcome assessment timing, and experimental settings. Thus, these aspects should be addressed while interpreting and comparing test data. In rodent research, the most consistently observed characteristic is the emergence of long-term mechanical and deep-tissue hypersensitivity, accompanied by converging alterations in monoaminergic modulation, neuroimmune and inflammatory signaling, spinal and supraspinal excitability, and peripheral metabolic and oxidative functions. This alignment of behavioral, neurochemical, electrophysiological, histological, and peripheral results offers biological validity to the paradigm, expanding beyond simply inducing nociceptive hypersensitivity. Conclusions: Using reserpine to evaluate fibromyalgia-associated pain biology is useful and mechanistically relevant. Behavioral, neurochemical, electrophysiological, histological, and peripheral data support the paradigm beyond nociceptive hypersensitivity.